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Degradation products of beclomethasone dipropionate in human plasma.
- Source :
- Drug Metabolism and Disposition; February 1998, Vol. 26 Issue: 2 p132-7, 6p
- Publication Year :
- 1998
-
Abstract
- The anti-inflammatory glucocorticosteroid beclomethasone dipropionate was found previously to degrade in human plasma at 37 degrees C to yield beclomethasone 17-monopropionate, beclomethasone 21-monopropionate, and beclomethasone together with three unknown species, D-1, D-2, and D-3. In this paper, we report the isolation of D-2 and D-3 by preparative HPLC and the elucidation of their structures. Both products D-2 and D-3 exhibited UV bathochromic shifts relative to beclomethasone dipropionate of 9 nm. From the mass spectrometry and 1H-NMR data, it is concluded that D-2 and D-3 are formed from beclomethasone and beclomethasone 21-monopropionate, respectively, with the loss of hydrogen chloride and the formation of a 9,11-epoxide. Data for 1H-NMR methyl chemical shifts are used to show that the epoxide has the mechanistically more plausible 9beta,11beta configuration. Thus, D-2 is 9beta, 11beta-epoxy-16beta-methyl-1,4-pregnadiene-17alpha,21- diol-3, 20-dione, and D-3 is its corresponding 21-propanoate. The various enzyme-catalyzed and nonenzyme-catalyzed reactions involved in the degradation of beclomethasone dipropionate in human plasma are discussed. A degradation scheme is proposed.
Details
- Language :
- English
- ISSN :
- 00909556 and 1521009X
- Volume :
- 26
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Drug Metabolism and Disposition
- Publication Type :
- Periodical
- Accession number :
- ejs5544532